title: Coupling of gene expression in medial prefrontal cortex and nucleus accumbens after neonatal ventral hippocampal lesions accompanies deficits in sensorimotor gating and auditory processing in rats.
abstract: BACKGROUND
  After neonatal ventral hippocampal lesions (NVHLs), adult rats exhibit evidence of neural processing deficits relevant to schizophrenia, including reduced prepulse inhibition (PPI) of acoustic startle and impaired sensory processing. In intact rats, the regulation of PPI by the ventral hippocampus (VH) is mediated via interactions with medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). We assessed PPI, auditory-evoked responses and expression of 7 schizophrenia-related genes in mPFC and NAC, in adult rats after sham- or real NVHLs.
  
  
  METHODS
  Male inbred Buffalo (BUF) rat pups (d7; n=36) received either vehicle or ibotenic acid infusion into the VH. PPI and auditory-evoked dentate gyrus local field potentials (LFPs) were measured on d56 and d66, respectively. Brains were processed for RT-PCR measures of mPFC and NAC Comt, Erbb4, Grid2, Ncam1, Slc1a2, Nrg1 and Reln.
  
  
  RESULTS
  NVHL rats exhibited significant deficits in PPI (p=0.005) and LFPs (p<0.015) proportional to lesion size. Sham vs. NVHL rats did not differ in gene expression levels in mPFC or NAC. As we previously reported, multiple gene expression levels were highly correlated within- (mean r's≈0.5), but not across-brain regions (mean r's≈0). However, for three genes--Comt, Slc1a2 and Ncam1--after NVHLs, expression levels became significantly correlated, or "coupled," across the mPFC and NAC (p's<0.03, 0.002 and 0.05, respectively), and the degree of "coupling" increased with VH lesion size.
  
  
  CONCLUSIONS
  After NVHLs that disrupt PPI and auditory processing, specific gene expression levels suggest an abnormal functional coupling of the mPFC and NAC. This model of VH-mPFC-NAC network dysfunction after NVHLs may have implications for understanding the neural basis for PPI- and related sensory processing deficits in schizophrenia patients.
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., Mail Code 0804, La Jolla, CA 92093-0804, USA. Electronic address: nswerdlow@ucsd.edu.
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., Mail Code 0804, La Jolla, CA 92093-0804, USA; Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Powell
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., Mail Code 0804, La Jolla, CA 92093-0804, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Breier
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., Mail Code 0804, La Jolla, CA 92093-0804, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Hines
authors.affiliation: Department of Psychiatry, UCSD School of Medicine, 9500 Gilman Dr., Mail Code 0804, La Jolla, CA 92093-0804, USA; Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Light
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000473:pathology*; D007051:Ibotenic Acid; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism; D009714:Nucleus Accumbens / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D000091042:Reelin Protein; D055139:Sensory Gating / Q000187:drug effects; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D000091042:Reelin Protein; C000717129:Reln protein, rat; D007051:Ibotenic Acid; D012697:Serine Endopeptidases
keywords: Catechol-O-methyltransferase; Medial prefrontal cortex; Nucleus accumbens; Prepulse inhibition; Schizophrenia; Ventral hippocampus